Cocaine abuse/dependence remains a major and public health problem and for a significant number of cocaine dependent individuals, current treatment interventions are ineffective. Finding a pharmacological treatment for cocaine abuse is an important elusive goal. The primary purpose of this grant is to developed safety data on a slow onset, long- active selective dopamine (DA) reuptake inhibitor being developed through the SPIRCAP mechanism for the treatment of cocaine dependence. Prior to the initiation of this research project, toxicity and pharmacokinetic studies will have been carried out with the test medication (Project 5). Because it is likely that individuals receiving a medication for the treatment of cocaine dependence may continue to use cocaine, particularly early in treatment, it is essential to determine whether this drug combination produces any adverse reactions. In this project, cocaine's physiological and psychological effects will be assessed after both acute and chronic administration of the test medication in cocaine abusing volunteers. Vital signs (heart rate, blood pressure, temperature, respiratory rate, oxygenation levels and ECG) will be monitored during each test session. Trained nurse observers will monitor participants and an adverse event symptom questionnaire will be administered at regular intervals. Complete physical exams and laboratory tests will be done before and after the study. In addition to providing safety data, this research will yield information about the efficacy of the test medication. We are hypothesizing that the dysphoria and craving associated with cocaine abstinence will be diminished by the test medication's DA reuptake blocking properties. It is also hypothesized that the test medication will produce positive mood changes as measured by the Profile of Mood States and the Addiction Research Center Inventory. This is a positive attribute for a treatment medication since it will enhance patient compliance with medication regimens. Finally, it is hypothesized that the test medication since it will enhance patient compliance with medication regimens. Finally, it is hypothesized that the test medication will attenuate the effects of cocaine that are mediated by DA through activation of autoreceptors. Activation of autoreceptors would be expected to decrease DNA synthesis rates and rates of DA neuronal firing. Because cocaine's effects are impulse-dependent, decreases in rate of firing of DA neurons should decrease cocaine's ability to elevate synaptic levels of DA. If no significant adverse events are found in these safety studies the test compound will be considered for a clinical trial in cocaine dependent research volunteers.